The aim of this study is to investigate the differences in mechanisms of action of psilocybin, the active ingredient in 'magic mushrooms', and the SSRI escitalopram for major depressive disorder.

All participants will have moderate-severe major depression and will receive two doses of psilocybin, three weeks apart. Psilocybin dosages will vary across the study. Some participants will also take escitalopram for 6 weeks (10mg for 3 weeks then 20mg for a further 3 weeks).

All participants will have their brains scanned before the first psilocybin dose and then 6 weeks later. There will be 7 study visits over the course of 3-4 months and participants will be expected to complete weekly questionnaires. There will also be a Skype interview 6 months after treatment and a few monthly questions.

Details:

We are looking for:

Participants who must:

Be aged 18-80

Have Unipolar major depression (moderate to severe degree)

Have no MRI contraindications (eg claustrophobia, metals in body)

Have no SSRI contraindications

Have a GP who can confirm diagnosis

Have no history of psychosis/mania or immediate family member with psychotic disorder

Agree to use accepted contraception methods/not planning pregnancy

Participants MUST NOT have the following conditions:

Diabetes

Epilepsy

Severe cardiovascular disease

Hepatic or renal failure

Location:

London

Expenses:

There are no financial incentives associated with this study. There may be costs associated with travelling to and from the study site which will fall to the participant (except on psilocybin dosing days, when a taxi will be booked by the team if required).